Alkamine esters of 1-aryl-2, 5-dialkylpyrrole-3, 4-dicarboxylic acids



Patented Oct. 24, 1950 ALKAMINE ESTERS OF 1- ARYL-2,5-DI- ALKYLPYB/ROLE3,4 DICARBOXYLIC ACIDS Ruth A. Walker, Manhasset, N. Y., and Jackson P.Sickels, Coral Gables, Fla., assignors to American Gyanamid Company, NewYork, N. Y., a corporation of Maine No Drawing. Application February 4,1948, Serial No. 6,336

11 Claims.

. This invention relates to mono and dialkamine esters of1-aryl-2,5-dialkylpyrole-3,4-dicarboxylic in which alk stands for alower alkyl radical and R stands for alkyl or all: C H N alk In thepast, a number of diethyl esters of l-alkyl 2,5- dimethyl pyrrole- 3,4-dicarboxylic acids have been prepared and also a diethyl ester of lcyclohexyl 2,5 dimethylpyrrole 3,4 dicarboxylic acid. These esters wereprepared by the standard method involving the Knorr synthesis. When itwas attempted to prepare the diethyl ester of1-aralkyl-l-2,5-diethylpyrrole-3,4- dicarboxylic acids the synthesisfailed. According to the present invention, it has been found possibleto prepare esters of l-aryl-2,5-dialkylpyrrole-3,4-dicarboxylic acids inwhich the alkyl groups may be not only methyl but also other alkylshaving a larger number of carbon atoms such as ethyl, propyl, etc. Theseesters may be transformed into the corresponding 3,4-dialkamine esterswhich latter are all new compounds and are useful for a number ofpurposes. Thus, for example, the esters in the form of their additionsalts with strong acids, such as hydrochlorides, exhibit localanesthetic power. The reason why it was found possible to prepare estersof 1-aryl-Z,5-dialkyl pyrrole-3,4-dicarboxylic acids in which the alkylgroups have more than one carbon atom whereas the same procedure failedin attempts to prepare corresponding l-aralkyl compounds has not beenfully determined and the present invention is not intended to be limitedto any particular theory with regard to this anomalous behavior.

The pyrrole dialkamine esters of the present invention may be preparedby catalysed alcoholysis of the corresponding pyrrole dialkyl esterswith a dialkylaminoalkanol, using a small amount of an alkali metalalcoholate as the catalyst. However, poor yields are generally obtainedby the ordinary alcoholysis procedure in which the esterand thedialkylaminoalkanol are heated together. Therefore, in order to getacceptable yields, it is necessary to employ a special procedure inwhich the reactants are permitted to stand at room temperature for anumber of hours, for example, overnight, before heating.

Another method for preparing the pyrrole dialkamine esters, which ispreferable in some respects, is to react the 1-aryl-2,5-dialkylpyrroie-3,4-dicarboxylic acid with a dialkylaminoalkyl chloride.

The latter method is also employed to prepare the mixed pyrrolealkamine-alkyl esters. The anhydride of the1-aryl-Z,5-dialkylpyrrole-3,4-dicarboxylic acid is reacted with analkanol, thus forming the monocarbalkoxy-monocarboxylic pyrrole, whichin turn is converted into the desired pyrrole mixed ester through itsreaction with a dialkylaminoalkyl chloride.

The method involving the use of a dialkylaminoalkyl chloride producesthe monoand dialkamine esters in the form of their hydrochlorides. Whenthe dialkamine esters are desired in this form, but are prepared by themodified, catalyzed alcoholysis, it is, of course, necessary to reactthe free bases with a strong mineral acid, such as hydrochloric, in theconventional manner in order to form the addition salt.

The 1-aryl-2,5-dialkyl-3,4-dicarbalkoxy pyrroles, which are the startingmaterials for the synthesis of the pyrrole alkamine esters of thepresent invention, are prepared by the wellknown Knorr synthesis. Thisgeneral reaction is described by Knorr, Berichte 18, 299 et seq. (1885),and involves the reaction of a diester of a diacylsuccinate with anaromatic amine. Some of the diacylsuccinates are known, such as thediacetosuccinates and the dipropionylsuccinates, but the otherdiacylsuccinates, such as the dibutyrylsuccinates, are new compounds.However, they may ,beprepared in the same manner as the knowndiacylsuccinates. Namely: an alkylmagnesium iodide is reacted with analkyl cyanoacetate and the complex formed between the Grignard reagentand the cyanoester is hydrolysed, yielding the corresponding beta-ketoester. The beta-keto ester is then converted to the sodium enolate byreacting it with metallic sodium in a suitablesolvent. The addition ofiodine to the resultant product causes the elimination of sodium iodideand the condensation of the enolate to the desired dialkyldiacylsuccinate.

While the above' described method of preparing the pyrrole dialkamineesters of the present invention is preferred, it should be understoodthat the invention is not limited thereto and in- 3 eludes the estersregardless of the method by which they are prepared.

The invention will be described in greater detail in conjunction withthe following specific examples:

Example 1 The dihydrochloride of the di (beta-diethylaminoethyl) esterof 1-pheny1-2,S-diethylpyrrole- BA-dicarboxylic acid Ca. C

Ten parts of ethyl dipropionylsuccinate was dissolved in twenty-fiveparts of glacial acetic acid and was reacted at an elevated temperaturewith three and one-half parts of anilline, producing1-phenyl-2,5-diethyl-3,4-dicarbethoxy pyrrole according to the usualKnorr synthesis. This product was drowned in water, filtered, andpurified by crystallization from petroleum ether, (M. P. 61-62" 0.).

Nine parts of l-phenyl--2,5-diethyl-3,4dicarbethoxy pyrrole was added toa solution of twotenths part of sodium in thirty parts ofbetadiethylaminoethanol. This reaction mixture was allowed to stand atroom temperature for fifteen hours and then the temperature was raisedto 165 C. and was maintained at this level for eight hours (the reactionvessel having been fitted with an efiicient fractionating column). Atthe beginning of the heating, ethanol distilled off very rapidly untilabout one and one-half parts of ethanol had come over, but during theremainder of the time only a small amount of additional ethanol wasremoved.

After the heating was completed, the pressure i on the system waslowered to mm. and the excess beta-diethylaminoethanol was distilledofi. The impure free base was converted to the hydrochloride by thefollowing procedure: The oily residue was dissolved in ether and theresultant solution was washed with water and then thoroughly dried. Asolution of dry hydrogen chloride in dry ether was slowly added, causingthe formation of a sticky precipitate. This product was repeatedlytriturated with dry ether and then further purified by reconversion tothe free base, using a alcohol potassium hydroxide solution andextracting the base into dry ether. The oily hydrochloride was againprecipitated by the slow addition of a solution of dry hydrogen chloridein dry ether to the ethereal solution of the base. The precipitate wasthen dissolved in chloroform and reprecipitated as a brown oil by theaddition of ether. This oil solidified on standing and finalpurification was effected by crystallization from dry amyl alcohol,which resulted in a white, crystalline product (M. P. 1'77.5-178.5 C.)The di(beta-diethylaminoethyl) ester of 1-phenyl-2,5-diethylpyrrole-3,4-dicarboxylic acid is hygroscopic, very soluble in water and in methylalcohol, .quite soluble in chloroform, and insoluble in ether.

The sodium used to catalyze the alcoholysis may be replaced by acorresponding amount of another alkali metal, such as potassium.

4 Example 2 The dihydrochloride of the di(beta-diethylaminoethyl) esterof 1-pheny1-2,5-diethylpyrrole- 3,4-dicarboxylic acid "can; CzH -HCICzHs CzHs

1-phenyl-2,5-diethyl-3,4-dicarbethoxy pyrrole was saponified by heatingit with alcoholic potassium hydroxide. A water solution of the potassiumsalt was then acidified with hydrochloric acid which precipitated thefree acid as a white flocculent solid (decomp. 264265 0.). Ten

parts of the pyrrole dicarboxylic acid was then dissolved in fifty partsof isopropanol and eleven and three-tenths parts ofbeta-diethylaminoethyl chloride was added. This reaction mixture wasrefluxed for fourteen hours and was then cooled to about 0 C. The dimerwhich had precipitated in small amount was filtered off and seventy-fiveper cent of the isopropanol was evaporated under vacuum. Dry ether wasthen added to the residue, precipitating the oily hydrochloride whichsolidified upon standing at a low temperature. The product was purifiedby crystallization from a chloroform-ether mixture, yielding a compoundwith the same melting point as that P produced in Example 1.

Example 3 The diyhdrochloride of the di(gamma-diethylaminopropyl) esterof 1-phenyl-2,5-diethyl- 40 pyrrole-3,4-dicarboxylic acid Six parts ofl-pheny1-2,5-diethylpyrrole-3,4-

dicarboxylic acid was added to fifty parts of dry isopropanol in areaction vessel provided with an efficient reflux condenser. Thesuspension was heated to the point of reflux while being vigorouslyagitated and then nine and one-half parts of gamma-diethylaminopropylchloride was gradually added. The temperature was then maintained atabout 95 C. for eighteen hours.

After. the reaction was complete, the isopropanol was distilled offunder vacuum until the reaction mixture had been reduced to abouttwentyfive per cent of its original volume. The residue was cooled to 0C. and dry ether was slowly added, precipitating an oily solid fromwhich the supernatant was decanted. This solid was then dissolved inchloroform and reprecipitated by the addition of dry ether. Finalpurification was accomplished by recrystallization from amyl alcohol.The diyhdrochloride of the di(gamma-diethylaminopropyl) ester of1-phenyl-2,5-diethylpyrrole-3,4-dicarboxylic acid was isolated in theform of fine white crystals (M. P. 114-115 C.) and possesses propertieswhich are similar to those of the correspondingdi-beta-diethylaminoethyl ester described in Examples 1 and 2.

Example 4 47:0-0 O CaHs Twelve parts of 1-phenyl-2,5,-diethylpyrrole-3,4-dicarboxylic acid and two hundred and fifty parts of aceticanhydride were heated together at 125 C. until the reaction wascomplete. Cooling and partial removal of the solvent under vacuum,caused the precipitation of the anhydride of 1 phenyl 2,5 diethylpyrrole3,4 dicarboxylic acid as fine white needles, which could be purified bycrystallization from ether. (M. P. 11254135 (3.).

Six parts of the anhydride described above and two and one-half parts ofabsolute ethyl alcohol were dissolved in fifty parts of dry pyridine andwere heated at 20 C. for about one day. The pyridine was then removedunder vacuum and two portions of absolute alcohol were successivelyadded to the residue and distilled off. The crude l phenyl 2,5 diethyl-3-carbethoxypyrrole-4-carboxylic acid was then purified byrecrystallization from methanol (M. P. l44145 0.).

Three and nine-tenths parts of the monoester described above wassuspended in fifty parts of dry isopropanol in a reaction vessel fittedwith a reflux condenser and an eflicient stirrer. The mixture was heatedto the point of reflux and then a solution of two and eight-tenths partsof gamma-diethyl-aminopropyl chloride in twentyfive parts of dryisopropanol was slowly added to the stirred suspension. The heating-(95C.) and the stirring were continued for about eighteen hours, duringwhich the pyrrole monoethyl ester went into solution.

After the reaction was complete, the volume of the mixture was reducedby about seventy-five percent by distilling off the isopropanol undervacuum. Dry ether was added to the cooled residual solution and acolorless oil separated immediately. which upon analysis proved to bethe desired hydrochloride of the gamma(diethylaminopropyl) ester of 1phenyl 2,5, diethyl 3- carbethoxypyrrole-4-carboxylic acid.

Example 5 The dihydrochloride of the di(beta diethylaminoethyl) ester of1 p tolyl 2,5 diethylpyrrole-3,4-dicarboxylic acid CzHs boxylic acid wasthen suspended in fifty parts of dry isopropanol and was reacted withfive and.

one-half parts of beta-diethylaminoethyl chlo-- ride in twenty-fiveparts of dry isopropanol, using the procedure described in Example 3.

After the reaction was complete, isopropanol was removed under vacuumuntil the volume of the reaction mixture had been reduced by half. Thesolution'was then cooled to 0 C. and the precipitated dimer was removedby filtration. The volume of solvent was further reduced under vacuumand dry ether was added to the residual solution until a light yellowoil separated out. The purification procedure described in Example 3 didnot cause this oil to crystallize, even after long standing, to a degreewhich would permit the isolation of the product as a sharp meltingsolid. However, analysis proved that the oil was the desireddihydrochloride of the di-betadiethylaminoethyl ester of1-p-tolyl-2,5-diethylpyrrole-3,4-dicarboxylic acid.

Example 6 V The dihydrochloride of the di(gamma-diethylaminopropyl)ester of l m tolyl 2,5 diethylpyrrole-3,4-dicarboxylic acid 3H3 o=c-o 0o omcmcmN .1101

c=c coo OHzCHzCHzN .1101

The procedure of Example 5 was followed, substituting meta-toluidine forpara-toluidine and gamma diethylaminopropyl chloride forbetadiethylaminoethyl chloride. The dihydrochloride of thedi(gamma-diethylaminopropy1) ester of 1- m tolyl 2,5 diethylpyrrole 3,4dicarboxylic acidwas obtained as an oil after being purified asdescribed in Example 3. This oil could be made to solidify upontrituration with dry acetone but the product was so hygroscopic that itcould be maintained in the solid state only when kept under completelyanhydrous conditions.

Example 7 The dihydrochloride of the di(beta diethylaminoethyl) ester of1 p -,chlorophenyl 2,5- diethylpyrrole-3,4-dicarboxylic acid 0:-COOCHCHN .1101

1 p chlorophenyl 2,5 diethyl: 3,4 dicarbethoxy pyrrole (M. P. 83-84 C.)was prepared according to the procedure used in Example 5, substitutingp-chloroaniline for p-toluidine in the Knorr synthesis. However, therewas one change in the general procedure employed in Example 5.beta-diethylaminoethyl chloride had been added to the isopropanolsolution of l-p-chlorophenyl- 2,5-diethylpyrrole-3,4 dicarboxylic acid(decomp. 244-245 (3.), the reaction mixture was allowed to stand at roomtemperature for a day before being refluxed for twenty hours. Thedihydrochloride of the di(beta-diethylaminoethyl)ester of 1 pchlorophenyl 2,5 diethylpyrrole 3,4-

.HCl

CaHs

dicarboxylic acid was obtained as a white solid After the isopropanolsolution of 7 (M. P. 180-182" C.), after purification andcrystallization from amyl alcohol. The product is hygroscopic, verysoluble in water and in methyl alcohol, quite soluble in chloroform, andinsoluble in ether.

Example 8 The dihydrochloride of the di(gamma-diethylaminopropyl) esterof 1 phenyl 2,5 dipropylpyrrole-3,4-dicarboxylic acid (3: 1C=CCOOCH:CH1OH1N Ethyl butyrylacetate was prepared by reacting eightyparts of ethyl cyanoacetate, dissolved in three hundred parts of dryether, with two and one-half times the theoretical amount ofnpropylmagnesium iodide. The n-propylmagnesium iodide was prepared bythe standard method for producing Grignard reagents, that is, the drymagnesium turnings were pretreated with iodine vapors and then reactedwith n-propyl iodide in ether solution. After the Grignard reagent hadbeen added to the ether solution of ethyl cyanoacetate, the reactionmixture was heated overnight at 70 C. Hydrolysis of the Grignard complexwas accomplishedby pouring the viscous, fluorescent mixture onto crackedice and carefully acidifying with sulfuric acid (1:1). The aqueoussolution was then repeatedly extracted with ether and the combined etherextracts were neutralized with sodium carbonate, washed with water anddried. The ether was then evaporated and the residual ethylbutyrylacetate was distilled under vacuum.

Sixty-three parts of ethyl butyrylacetate dissolved in dry ether wasslowly added to ten parts of sodium sand suspended in dry ether. A gummymass was formed, which, after standing overnight at room temperature,was treated with fifty parts of iodine dissolved in a large volume ofdry ether. When the reaction was complete, the iodine color remained inthe reaction mixture and then the sodium iodide was filtered ofi.Decolorization of the ether solution with sodium carbonate andevaporation of the solvent left a mixture of the oily and thecrystalline diethyl dibutyrylsuccinates. Solid diethyldibutyrylsuccinate (M. P. 81-8l.5 C.) was obtained upon crystallizationfrom ethanol, acetone, or ethyl acetate.

The diethyl dibutyrylsuccinate was then reacted with aniline in boilingglacial acetic acid, according to the standard conditions for the Knorrsynthesis. The l-phenyl-2,5-dipropyl-3,4- dicarbethoxy pyrrole thusprepared was purified and crystallized from petroleum ether (M. P.'73.5-'74.5 C.).

This pyrrol dialkyl ester was converted to the dissolved in twenty-fiveparts of dry isopropanol was slowly added to the stirred suspension.After the addition of the chloride, the reaction mixture was heated atC. for about sixteen hours, until the reaction was substantiallycomplete.

The volume of isopropanol was then reduced by about seventy-five percentby distilling off the solvent under vacuum. The addition of dry ether tothe cooled, residual solution caused the precipitation of the white,oily hydrochloride. The dihydrochloride of thedi-gamma-diethylaminopropyl ester of l phenyl 2,5dipropylpyrrole-3,4-dicarboxylic acid was further purified andcrystallized from amyl alcohol, yielding fine, white crystals (M. P.2l'7-218 C.). This product is solubl in water, in methyl alcohol, and inchloroform, and is insoluble in ether.

Example 9 The dihychloride of the di(gamma-diethylaminopropyl) ester of1-p-tolyl-2,5-dipropylpyrrole-3,4-dicarboxylic acid CzHl 3:COOCHzCHzCHzN .HCl C3117 C2115 1-p-toly1-2,5-dipropyl-3,4-dicarbethoxypyrrole M. P. 93.5-94.5 C.) was prepared according to the procedure usedin Example 8, substituting p-toluidine for aniline in the Knorrsynthesis. However, there was one change in the general procedureemployed in Example 8. After the isopropanol solution ofgamma-diethylaminopropyl chloride had been added to the isopropanolsolution of l-p-tolyl-2,5-dipropylpyrrole-3,4-dicarboxylic acid (decomp.l47-148 C.), the reaction mixture was allowed to stand at roomtemperature for twenty-four hours before being refluxed at 95 C. foreighteen hours. The dihydrochloride of the di(gamma-diethylaminopropyl)ester of l-p-tolyl-2,5-dipropylpyrrole-3,4- dicarboxylic acid, thusproduced, did not crystallize as rapidly as the corresponding phenylcompound. However, analysis proved that the oil was the desired product.It is very hygroscopic, is soluble in alcohol and in chloroform, and isinsoluble in ether.

Example 10 The dihydrochloride of the di(gamma-diethylaminopropyl) esterof 1-p-chloropheny1-2,5-dipropylpyrrole-3,4-dicarboxylic acid chloridewas an oil which analysis proved to be the desired hydrochloride. Thedihydrochloride of the di(gamma-diethylaminopropyl) ester of 1 pchlorophenyl -4.2',5 dipropylpyrrole 3,4- dicarboxylic acid is veryhygroscopic and is soluble in alcohol and in chloroform, and insolublein ether. 1 Example 11 The dihydrochloride of thedi(beta-diethylaminoethyl) esterof1-phenyl-2,5-dimethylpyrrole-3,4-dicarboxylic acid 91 parts of thediethyl ester of 1-phenyl-2,5- dimethylpyrrole-3,4-dicarboxylic acid,(prepared by reacting a glacialacetic acid solution of symmetricaldiethyl diacetosuccinate with a slight excess of aniline), was added to455 parts of betadiethylaminoethanol in which 1 to 2 parts of metallicsodium was then dissolved. The reaction mixture was heated in a vesselprovided with an efiicient fractionating column until it refluxed to thetop of the column. The temperature rose to about 159. The refluxing wascontinued for many hours until the reaction was substantially completeat which time the excess beta-diethylaminoethanol was removed by vacuumdistillation. The residue was dissolved in ether, washed with water, theether solution dried and an ether solution of hydrogen chloride added.The hydrochloride which was precipitated was dissolved in water andsaponified with potassium hydroxide to form the free base which wasextracted with ether. After drying and removing the solvent, the freebase remained as a residual oil which was distilled oil under 2 mm.pressure. The bulk of the material distilled over at 260-270 C.

The free base was re-dissolved in ether and the hydrochlorideprecipitated by adding an ether solution in hydrogen chloride. Afterrecrystallization from butanol, the dihydrochloride of thedi(beta-diethylaminoethyl) ester of 1-phenyl-2,5-dimethylpyrrole-3,4-dicarboxylic acid was obtained as a graymicrocrystalline powder, melting at 185-188.5 C. (uncorr.)

Example 12 The product of Example 11 was produced by an alternateprocess. The diethyl ester of l-phenyl-2,5-dimethylpyrrole-3,4-dicarboxylic acid was transformed into thecorresponding potassium salt by means of alcoholic potassium hydroxidesolution, separating the salt by filtration.

68 parts of the potassium salt were treated with 160 parts of thionylchloride by heating to 50 C. with vigorous agitation for a number ofhours until the salt had been transformed into the acid chloride. thendistilled off in a low vacuum, the residue dissolved in benzene andfiltered free from potassium chloride. To the benzene solution there wasthen added 100 parts of beta-diethylaminoethanol and the mixture heatedfor a number of hours at 50 C. until reaction was complete. Water andexcess potassium hydroxide were then added and the product extractedwith ethe and dried. A residual oil was obtained which had substantiallythe same boiling point as that produced in Example 11. On transformationinto the hydrochloride by the procedure described in the same exampleand recrystallization from butanol, a product was obtained which wasiden- The excess thionyl chloride was 10 tical with that produced byample. v

In the examples, the dihydrochloride has been produced as an end'product since this is the form in which the products are useful aslocalanesthetics. In the examples describing theprocess of producing theesters by catalyzed alcoholysis, the free base is produced first. Whenthe preferred method using the dialkylaminoalkyl chloride is followed,the dihydrochloride is produced in the first instance. These hydrochlorides may be transformed into the free bases by neutralization withalkali in the conventional manner. The free bases are the form in whichthe esters affect the activity of rubber accelerators.

In the examples, the hydrochlorides of the esters have been described asthe salts of strong mineral acids as this is the most commonly usedmineral acid for formation of addition salts with amines; Other strongmineral acids such-as hydrobromic acid form the corresponding salts andare, of course, included in the broader aspects of the presentinvention.

In most of the examples the final step has been carried out in dryisopropanol. The nature of the alcohol does not exert any particulareffect on the reaction. Any of the other lower aliphatic alcohols may beused, such as the butyl alcohols, normal propanol, etc. Isopropanol ispreferred for one reason only, and that is that its boiling point is atabout the temperature at which the reaction proceeds most smoothly. Itcan, therefore, be used as an accurate thermostat by operating under areflux. This might be considered purely as a mechanical advantage ofusing isopropanol and the invention is in no sense limited to processesusing this preferred alcohol as a solvent.

The most common dialkylaminoalkanols and chlorides are thediethylaminoalkanols and their chlorides. These have been described inthe examples and are preferred. However, the alkyl group on the nitrogenis not a particularly critical part of the molecule as far as thepreparation of the compounds is concerned and the corresponding dipropylor dibutylaminoalkyl esters may be prepared, substituting betadipropylor dibutylaminoethyl chloride for beta or gamma dipropylordibutylaminopropyl chloride for the gamma diethylaminopropyl chloride.In its broader aspects the invention includes these other alkamineesters, but for most practical purposes the diethylaminoalkyl chloridesare more readily available and produce the most effective compounds.These are, therefore, preferred.

We claim:

1. Compounds selected from the group consisting of esters ofl-monocyclic aryl-2,5-dialky the preceding ex+ pyrrole-3,4-dicarboxylicacids with dialkylaminoalkanols and the addition salts of the esterswith strong acids.

2. Compounds selected from the group consisting of esters ofl-monocyclic aryl-2,5-dialkylpyrrole-3,4-dicarboxylic acids withdiethylaminoalkanols and the addition salts of the esters with strongacids.

3. Compounds selected from the group consisting of esters ofl-rnonocyclic aryl-2,5-dialkylpyrrole-3/l-dicarboxylic acids with betadiethylaminoethanol and the addition salts of the esters with strongacids.

4. Compounds selected from the group consisting of esters ofl-monocyclic aryl-2,5-dialkyl- '11 pyrrole-3,4-dicarboxylic acids withgamma diethylaminopropanoland the addition salts of the esters withstrong acids.

5. Compounds according to claim 1 in which the alkyl groups on the 2 and5 carbon atoms of the pyrrole ring are methyl.

6. Compounds according to claim 1 in which the alkyl groups on the 2 and5 carbon atoms of the pyrrole ring are ethyl.

'7. Compounds according to claim 1 in which the alkyl groups on the 2and 5 carbon atoms of the pyrrole ring are propyl.

8. Compounds according to claim 1 in which the l-ar'yl group is phenyl.

9. Compounds according to claim 1 in which the l-aryl group is tolyl.

10. Compounds according to claim 1 in which the l-aryl group isp-chlorophenyl.

11. A method of preparing dihydrohalides of esters of l-monocyclicaryl-2,5-dialkylpyrrole- 3,4-dicarboxy1ic acids withdialkylaminoalkanols 7 which comprises reacting the correspondingdialkylaminoalkyl halide with the corresponding 1- mononucleararyl-2,5-dia1kylpyrrole-3,4-dicarboxylic acids.

RUTH A. WALKER. JACKSON P. SICKELS.

REFERENCES CITED The following references are of record in the file ofthis patent:

UNITED STATES PATENTS January 1946, vol. 18, pages 161 and 171.

1. COMPOUNDS SELECTED FROM THE GROUP CONSISTING OF ESTERS OF1-MONOCYCLIC ARYL-2.5-DIALKYLPYRROLE-3,4-DICARBOXYLIC ACIDS WITHDIALKYLAMINOALKANOLS AND THE ADDITION SALTS OF THE ESTERS WITH STRONGACIDS.